Rotavirus is the most common cause of diarrhea in children; nearly every child in the world has been infected with a rotavirus by the age of five. The virus is believed to be highly contagious by the fecal-oral route, and affects no particular socioeconomic or geographic group disproportionately. While the majority of children survive infection, a large number of children become severely ill, and the number of deaths associated with the virus is considerable. In addition to its impact on human health, rotavirus also infects animals, and is a pathogen of livestock.
Rotavirus A accounts for more than 90% of rotavirus gastroenteritis in humans. Rotavirus A is an icosahedral virus in the family Reoviridae with a distinct hub-and-spoke morphology. Rotavirus particles contain three protein layers surrounding the viral genome which consists of 11 segments of double-stranded RNA, each segment encoding a protein. There are six viral proteins (VPs) that form the virus particle, called VP1-VP7, and six nonstructural proteins (NSPs), called NSP1-NSP6. Rotaviruses are classified by group, subgroup and serotype according to properties characteristic of the viral capsid proteins.
A number of the structural proteins are particularly important in eliciting an immune response in a host since these proteins are present on the outermost surface of the viral particles. It is believed that VP7 and VP4 play an important role in the host immune response. Variants of VP7 and VP4 structural proteins characterize distinct rotavirus A serotypes. In particular, variants of human VP7 are identified as “G” serotypes including at least serotypes G1, G2, G3, G4, G5, G6, G8, G9, G10, G11, G12, G13 and G14. Variants of the VP4 structural protein are identified as “P” serotypes including P1A, P1B, P2A, P3, P4, P5, P6 and P8. Because intact rotaviruses are characterized by both a VP7 protein and a VP4 protein, individual virus serotypes are named according to the identity of the variant of these two proteins contained in the particular virus. The G1 serotype of rotavirus A is the most common serotype associated with human disease worldwide. A common rotavirus A contains both G1 and P[8] variants of VP7 and VP4, and is called G1P[8]. A number of vaccines have been developed which use rotavirus A G1 strains with the goal of developing immunity in a host against rotavirus A G1 strains as well as rotavirus A strains having other serotypes.
A diversity of human rotavirus types is increasingly recognized as contributing to acute severe diarrhea disease worldwide. This diversity underscores the need for robust vaccines capable of generating immunity against several strains. ROTARIX® is a vaccine that has broad cross-reactive immunity and cross protection against homotypic Wa-like and heterotypic DS-1 like strains among children worldwide. However, this vaccine confers lower efficacy against DS-1 like strains in some regions. Thus, there is a continuing need for vaccines against human rotavirus A of both common and less common types.